The overall goal of this project is to use cryopreserved nonhuman primate embryos and ovariectomized rhesus monkeys to develop a hormonally controlled, spayed monkey model for studies of implantation, embryonic development and early pregnancy in primates. There is no valid in vitro model that would permit similar studies in any mammal. Many aspects of primate implantation are unique and must be studied in primate species. The research proposed will evaluate the effects of various hormonal treatments on implantation rates of rhesus monkey embryos produced by in vitro fertilization (IVF) and cryobanked before embryo transfer, and will establish the minimal hormonal requirements for implantation. Data will be obtained to determine whether a follicular phase estradiol surge is essential for implantation, whether estradiol is needed during the luteal phase, and the minimum level of progesterone required to support implantation. These studies will provide novel information on the requirements for implantation in primates, will allow rigorous analysis of the systemic and local requirements for establishment and maintenance of pregnancy in nonhuman primates, will permit implantation of experimentally manipulated preimplantation embryos, and will have high relevance to the human IVF experience, especially in cases of agonadal women receiving donor embryos. The specific aims are to first validate a standard in vivo model of implantation, including comparison of intraoviductal versus transcervical routes of transfer, and the role of the preovulatory estradiol surge; and then to determine the minimal amounts of progesterone and estradiol needed to support implantation and the establishment of pregnancy. Once these parameters are validated this in vivo model of pregnancy will provide a major new opportunity to investigate how embryo quality. oviductal milieu, and endometrial development affect implantation because each could be experimentally altered under controlled conditions. The system will provide an unprecedented opportunity to utilize gene transfer technology and gene therapy approaches to investigate primate embryo development at the cellular and molecular levels and will permit entirely novel research into the critical components of the early developmental process in nonhuman primates.